Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02659020




Registration number
NCT02659020
Ethics application status
Date submitted
15/01/2016
Date registered
20/01/2016

Titles & IDs
Public title
A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Scientific title
A Phase 1b (Open-Label)/Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma
Secondary ID [1] 0 0
I5B-MC-JGDL
Secondary ID [2] 0 0
15839
Universal Trial Number (UTN)
Trial acronym
ANNOUNCE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaratumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Docetaxel
Treatment: Drugs - Placebo

Experimental: Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel - Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m\^2) on days 1, 8 plus docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Experimental: Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel - Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).

Experimental: Phase 2: Olaratumab + Gemcitabine + Docetaxel - Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.

Placebo comparator: Phase 2: Placebo + Gemcitabine + Docetaxel - Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.


Treatment: Drugs: Olaratumab
Administered IV

Treatment: Drugs: Gemcitabine
Administered IV

Treatment: Drugs: Docetaxel
Administered IV

Treatment: Drugs: Placebo
Administered IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
Assessment method [1] 0 0
A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0:

1. Febrile neutropenia with documented Grade =3 infection or sepsis
2. Grade 4 neutropenia lasting 7 days or longer.
3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.
4. Nonhematologic Grade =3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea that can be controlled with optimal medical management within 48 hours.
Timepoint [1] 0 0
Cycle 1 (Up To 21 Days)
Primary outcome [2] 0 0
Phase 2: Overall Survival (OS) (Olaratumab-Naive)
Assessment method [2] 0 0
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Timepoint [2] 0 0
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary outcome [1] 0 0
Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Assessment method [1] 0 0
Cmax of Olaratumab.
Timepoint [1] 0 0
Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
Secondary outcome [2] 0 0
Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Assessment method [2] 0 0
Cmin of Olaratumab.
Timepoint [2] 0 0
Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1
Secondary outcome [3] 0 0
Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
Assessment method [3] 0 0
T1/2 of Olaratumab.
Timepoint [3] 0 0
Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
Secondary outcome [4] 0 0
Phase 1b/2: PK: Cmax of Gemcitabine
Assessment method [4] 0 0
Cmax of Gemcitabine.
Timepoint [4] 0 0
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Secondary outcome [5] 0 0
Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-8]) of Gemcitabine
Assessment method [5] 0 0
AUC\[0-8\] of Gemcitabine
Timepoint [5] 0 0
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Secondary outcome [6] 0 0
Phase 1b/2: PK: Cmax of Docetaxel
Assessment method [6] 0 0
Cmax of Docetaxel.
Timepoint [6] 0 0
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Secondary outcome [7] 0 0
Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-8]) of Docetaxel
Assessment method [7] 0 0
AUC \[0-8\] of Docetaxel.
Timepoint [7] 0 0
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Secondary outcome [8] 0 0
Phase 1b/2: Population PK: Clearance of Olaratumab
Assessment method [8] 0 0
Population PK: Clearance of Olaratumab
Timepoint [8] 0 0
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Secondary outcome [9] 0 0
Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
Assessment method [9] 0 0
The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).
Timepoint [9] 0 0
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Secondary outcome [10] 0 0
Phase 2: Overall Survival (Olaratumab Pre-Treated)
Assessment method [10] 0 0
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Timepoint [10] 0 0
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary outcome [11] 0 0
Phase 2: Progression Free Survival (PFS)
Assessment method [11] 0 0
PFS was defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 \[RECIST v.1.1\]) or death due to any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.
Timepoint [11] 0 0
Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
Secondary outcome [12] 0 0
Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
Assessment method [12] 0 0
ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Timepoint [12] 0 0
Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
Secondary outcome [13] 0 0
Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
Assessment method [13] 0 0
DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Timepoint [13] 0 0
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
Secondary outcome [14] 0 0
Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
Assessment method [14] 0 0
The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf "worst pain score" (TWP) was defined as the time from the date of randomization to the first date of either a "worst pain" score increase of greater than or equal to (=) 2 points from baseline or an analgesic drug class increase of =1 level. If the patient has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered.
Timepoint [14] 0 0
Baseline to Follow-up (Up To 24 Months)
Secondary outcome [15] 0 0
Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.
Assessment method [15] 0 0
The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems.
Timepoint [15] 0 0
Baseline to Follow-up (Up to 33 months)
Secondary outcome [16] 0 0
Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
Assessment method [16] 0 0
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.
Timepoint [16] 0 0
Cycle 1 (Day 1), Follow-up (Up to 38 Months)
Secondary outcome [17] 0 0
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Assessment method [17] 0 0
Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies
Timepoint [17] 0 0
Baseline through Follow-Up (Up to 38 Months)

Eligibility
Key inclusion criteria
* The participant may have no more than 2 prior lines of systemic therapies (neoadjuvant and adjuvant therapies will not be considered as a prior line of therapy) for advanced or metastatic disease and is suitable to receive gemcitabine and docetaxel therapy. All previous therapies must have completed = 3 weeks (21 days) prior to first dose of study drug.
* In the Phase 2 part, prior olaratumab/doxorubicin combination therapy in 1 prior treatment line is allowed.

* Prior olaratumab therapy must have been received with doxorubicin as indicated on the olaratumab label.
* Prior olaratumab therapy must have included at least 2 full cycles of olaratumab/doxorubicin (that is, a minimum of 4 doses of olaratumab).
* Participants, who completed at least 2 cycles of combination olaratumab/doxorubicin therapy then discontinued doxorubicin due to toxicity or maximum dosing and proceeded to olaratumab monotherapy, are eligible.
* The most recent dose of olaratumab must have been received within 180 days of randomization in this study.
* Availability of tumor tissue is mandatory for study eligibility. The participant must have consented to provide archived formalin-fixed paraffin-embedded tumor tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor tissue for future central pathology review and translational research (if archived tissue is unavailable).
* The participant has adequate hematologic, organ, and coagulation function within 2 weeks (14 days) prior to enrollment (Phase 1b) or randomization (Phase 2).
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* The participant is diagnosed with gastrointestinal stromal tumor (GIST) or Kaposi sarcoma.
* The participant has active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment (Phase 1b) or randomization (Phase 2). Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment (Phase 1b) /randomization (Phase 2) to rule out brain metastasis.
* The participant has received prior treatment with gemcitabine or docetaxel. Note: Participants previously enrolled in the I5B-MC-JGDJ (NCT02451943) or any other blinded study with olaratumab are not eligible to participate in this trial.
* The participant has electively planned or will require major surgery during the course of the study.
* Females who are pregnant or breastfeeding.
* The participant has an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Lille Cedex
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Württemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Brandenburg
Country [24] 0 0
Germany
State/province [24] 0 0
Niedersachsen
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Hungary
State/province [26] 0 0
Szolnok
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Israel
State/province [28] 0 0
Haifa
Country [29] 0 0
Israel
State/province [29] 0 0
Petah Tiqva
Country [30] 0 0
Israel
State/province [30] 0 0
Tel Aviv
Country [31] 0 0
Italy
State/province [31] 0 0
Torino
Country [32] 0 0
Poland
State/province [32] 0 0
Warszawa
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Greater London
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Merseyside
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.